(637) Donor-Derived Cell Free DNA (dd-cfDNA) in Pregnant Kidney Transplant Recipients

Thursday, February 9, 2023

4:00 PM – 5:30 PM

Objective: Distinguishing between allograft rejection, kidney disease progression, and preeclampsia in a non-invasive manner can be difficult in pregnant kidney transplant recipients. Donor-derived cell-free DNA (dd-cfDNA) is a biomarker that can be measured non-invasively to assess risk of allograft rejection. However, using dd-cfDNA to monitor allograft status in pregnant kidney transplant recipients requires distinguishing between fetal, donor, and recipient cfDNA fragments. In this study, we aimed to measure dd-cfDNA in a cohort of pregnant kidney transplant recipients using a combination of NIPT and transplant monitoring technology utilizing cfDNA.

Study Design: dd-cfDNA was measured in 6 pregnant kidney recipients as shown in Figure 1. Identification of SNPs at which both the mother and father were homozygous ensured homozygosity of the fetus and that heterozygosity observed in the maternal cfDNA originated from the allograft. These SNPs were used to calculate donor fraction estimates (DFE). Clinical data collected included kidney function test, mode of delivery, preeclampsia, and preexisting hypertension.

Results: DFE was calculated for 4/6 pregnant kidney transplant recipients. 5/6 of these patients had preexisting chronic hypertension and 4/6 had superimposed preeclampsia. All patients underwent medically indicated inductions of labor and subsequent cesarean births for varied indications. Chart review also revealed that all patients experienced a spike in serum creatinine and acute kidney injury during the study either before, after, or during delivery.

Conclusion: In this proof-of-concept study, we demonstrate that dd-cfDNA can be measured in pregnant kidney recipients that have chronic kidney dysfunction. These measurements can help differentiate between acute rejection and hypertensive diseases of pregnancy. A larger cohort study will be needed to define the utility of longitudinal monitoring during pregnancy to help inform the physician in clinical decision making that can affect both allograft outcomes and maternal fetal health.

Primary Author(s)

Jessica Tang, PhD (she/her/hers)
Senior Scientist
Natera
Natera, California, United States

Coauthor(s)
KW
Kate Woodruff, BS, PhD
Senior Data Scientist
Natera
Natera, California, United States

CJ
Christine Jang, MD
University of California, Los Angeles
Los Angeles, California, United States

NC
Nicole Charland, BS
Medical Student
University of California, Los Angeles
Los Angeles, California, United States

LB
Lauren Bass, BS
Staff Research Associate
University of California, Los Angeles
Los Angeles, California, United States

PV
Phikhanh Vu, BS
Senior Research Associate
Natera
Natera, California, United States

CS
Christopher Sotto, BS, MS
Clinical Research Scientist
Natera
Natera, California, United States

EA
Ebad Ahmed, BS, MS, PhD
Associate Director, Data Science
Natera
Natera, California, United States

PV
Paul Van Hummelen, BS, PhD
Associate Director, Research
Natera
Natera, California, United States

GH
Gabrielle Heilek, BS, PhD
Vice President, Research and Development Organ Health and Women's Health
Natera
Natera, California, United States

BZ
Bernhard Zimmermann, BS, MSc, PhD
Chief Scientific Officer and Senior Vice President
Natera
Natera, California, United States

SB
Suphamai Bunnapradist, BS, MD, MS
Professor of Clinical Medicine, Nephrologist
University of California, Los Angeles
Los Angeles, California, United States

HT
Hossein Tabriziani, BS, MD
Director of Organ Transplant
Natera
Natera, California, United States

Presenting Author(s)

Yalda Afshar, MD, PhD (she/her/hers)
Assistant Professor
University of California, Los Angeles
Los Angeles, California, United States